Morphological studies on periodontal disease in the cynomolgus monkey

Electron microscopic observations were made on naturally occurring gingivitis, on gingivitis at non-ligated sites of an experimental animal, and on ligature-induced periodontitis in a periodontal disease model using female cynomolgus monkeys.
For both types of gingivitis specimens, a plaque associated chronic inflammatory reaction was observed, comparable to that described for the human established lesion. Bacterial accumulations on tooth surfaces were separated from the epithelium by neutrophils which exhibited variations in fine structure and extent of bacterial phagocytosis related to their proximity to the plaque. In the inflamed connective tissue of the papillae, collagen was reduced to strands extending between the cellular elements. The plasma cell was the most common inflammatory cell and had three major variations in form.
With ligature-induced periodontitis, similar inflammatory features were observed in the gingiva. A complex flora like that encountered in human periodontitis was observed around and within the ligature as well as more apically in the pocket. As compared to the flora in gingivitis, more spirochetes were encountered, a larger proportion of the microorganisms appeared to be in a living state, and bacteria were in contact with the epithelial surface, rather than being walled off by the neutrophils. This seemingly more aggressive plaque was associated with an advanced lesion characterized by changes that indicated sequential destruction of the collagenous attachment to cementum and concommitant apical migration of the epithelial attachment. No bacteria were observed in the soft tissues, even in the wide intercellular spaces between the epithelial cells.     

Preventing rubella: assessing missed opportunities for immunization.

Cases of rubella continue to occur among adults in the United States because 10-20 per cent of persons in this age group remain susceptible. To evaluate the potential preventability of these cases, we present a method for assessing missed opportunities for rubella immunization, based on immunization recommendations of the Immunization Practices Advisory Committee (ACIP) of the US Public Health Service (PHS). Immunization programs faced with limited resources can use analysis of missed opportunities to focus on those gaps in implementation contributing most to the remaining rubella cases.     

Haematological changes due to triathlon competition.

A twelve parameter blood cell profile has been measured in 6 subjects before and after each phase of triathlon event. This involved 29 miles cycling, 12 miles running and finally 18.5 miles canoeing. There was a significant decrease in plasma volume (8.7% +/- 3.1%, p less than 0.001) following the first phase (cycling); this decrease was sustained to the end of the event. A substantial increase in the number of circulating leukocytes after cycling (84 +/- 58%) and running (255 +/- 83% of pre-event value) was observed. There was no further leucocyte increment after the canoeing stage which may indicate that the circulating concentration of these cells was maximal after running. Fluid shifts following the postural alteration accompanying the different types of exercise and subject variability may have masked any subtle changes in the red cell parameters.     

Mechanistic studies of the phototoxic potential of PD 117596, a quinolone antibacterial compound.

PD 117596 is a novel quinolone compound that is being investigated for use as an antibacterial agent. Early investigations demonstrated a significant phototoxic liability associated with this compound. These studies were undertaken to investigate the mechanism of phototoxicity using an in vitro model. In the UVA region, PD 117596 was found to be a more efficient producer of singlet oxygen than rose bengal, ciprofloxacin, nalidixic acid, or PD 118879, another quinolone under investigation. The quantum yield of photoreaction for PD 117596 was relatively low (phi = 0.021); however, it was approximately 10-fold higher than other tested quinolones. In vitro studies using a mouse erythrocyte model were used to further investigate the mechanism of phototoxicity. PD 117596-induced photohemolysis was found to be oxygen dependent with a relatively rapid onset that progressed even after removal of light. Preirradiation of the compound prevented subsequent hemolytic or photohemolytic action. BHA, BHT, alpha-tocopherol, and the iron chelator DTPA were all found to be effective at ameliorating the photohemolytic response. The photohemolytic response was markedly enhanced when D2O was substituted for H2O in the incubation medium, indicating a singlet oxygen-mediated mechanism of action. A rise in thiobarbituric acid products was noted within 1 hr of irradiation and was maximal at the time of onset of overt photohemolysis. These data suggest that singlet oxygen production by irradiated PD 117596 is responsible for secondary changes in mouse red blood cells including lipid peroxidation and ultimately results in cellular lysis.     

The safety and cost-effectiveness of low osmolar contrast media. Can economic analysis determine the real worth of a new technology?

OBJECTIVES: To estimate the reduction in mortality associated with a reduced adverse reaction rate following the substitution of older high osmolar radiocontrast media (HOCM) by the newer and more expensive low osmolar contrast media (LOCM), and to assess the cost-effectiveness of switching from HOCM to LOCM in patients with and without underlying risk factors for adverse reactions from radiocontrast agents. DATA SOURCES: Data from large prospective studies of adverse reactions to HOCM and LOCM were used to estimate the expected number of deaths and severe non-fatal reactions in a hypothetical population receiving one million intravenous radiocontrast injections with HOCM, and the expected reduction in the frequency of these outcomes after substitution by LOCM in high-risk and low-risk groups respectively. Life-years lost with each radiocontrast-related death were estimated from an audit of fatal adverse reaction reports submitted to the Adverse Drug Reactions Advisory Committee. The direct costs considered in the study were the increased costs of LOCM and the hospital costs of treating radiocontrast reactions which were estimated from an audit of cases admitted to public hospitals in Newcastle. STUDY SELECTION: The literature search included Medline (1966-1989) and bibliographies of original and review articles. We included only studies which were prospective, monitored patients in a formal way, described a mechanism for the recording of adverse events and were of sufficient size to have been capable of detecting severe reactions to radiocontrast agents. DATA EXTRACTION: Data were extracted independently by two investigators, unblinded, with disagreements resolved by consensus. DATA SYNTHESIS: Mortality data from individual reports were pooled and exact confidence intervals were calculated on the assumption of a Poisson distribution. In the case of comparative studies the relative risks of severe reactions in low-risk versus high-risk patients and with LOCM compared with HOCM were treated for homogeneity, and pooled odds ratios and 95% confidence intervals (CI) were calculated by combining the logarithms of the odds ratios weighted by their variances. RESULTS: The mortality after intravenous administration of HOCM was estimated from all studies to be 23.3 (95% CI, 2.4-33.1) per million injections. However, the mortality was 11.7 per million (95% CI, 2.4-34.1) in studies published since 1986. The mortality after the use of LOCM was estimated as 3.9 per million (95% CI, 0.1-21.7).(ABSTRACT TRUNCATED AT 400 WORDS)     

Fatal streptokinase-induced intracerebral haemorrhage in cerebral amyloid angiopathy

A fatal intracerebral haemorrhage (ICH) associated with streptokinase (SK) treatment of an acute myocardial infarction is described. Autopsy examination showed a lobar ICH and severe cerebral amyloid angiopathy (CAA). The close temporal relationship between SK administration and intracranial haemorrhage, the absence of pretreatment risk factors for ICH, and the presence of CAA suggests that these are related phenomena. Accordingly: 1. There may be a synergistic relationship between CAA and intracranial haemorrhage induced by fibrinolytic agents; 2. Thrombolytic agents may induce more frequent than expected intracranial haemorrhage in conditions associated with a high incidence of CAA, notably old age and Alzheimer's disease; 3. A regional defect in haemostasis other than vessel fragility may contribute to the intracranial haemorrhagic predisposition of CAA; 4. Autopsy examination of cases of ICH is an essential part of the audit of clinical trials of fibrinolytic agents.